Is Helicobacter pylori eradication a cost-effective treatment of duodenal ulcer disease?

Treatment strategies aimed at eradicating Helicobacter pylori have shown positive results in the management of duodenal ulcer disease. Several cost-effectiveness studies comparing these regimens with traditional therapy have recently been conducted, and results are discussed in this review. Cost comparisons of different treatment strategies cannot be performed without first identifying whether the cost of ulcer diagnosis is included in the study. Assuming that only 20% of patients with dyspepsia actually have ulcer disease, costs may vary, depending on the study population. Importantly, treatment costs should not be compared between a patient population with confirmed ulcer disease and one without confirmed disease. In patients with confirmed ulcer disease, studies consistently show that H. pylori eradication strategies are associated with greater efficacy and lower costs than traditional treatment, and are therefore a more cost-effective alternative to standard therapy. Although all models used in the cost-effectiveness analyses assume that patients discontinue treatment following successful eradication of the microorganism, in clinical practice some patients continue antisecretory treatment beyond this period. Thus, savings as a result of H. pylori eradication may be less substantial than indicated in cost-effectiveness studies.     

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

Background:

Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers.

Methods:

Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a ¹³C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole.

Results:

195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P = 0.31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P = 0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups.

Conclusion:

Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

     

Is eradication sufficient to heal gastric ulcers in patients infected with Helicobacter pylori? A randomized,controlled, prospective study

BACKGROUND: In Helicobacter pylori infection, the effect of short-term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known. AIM: To compare 1-week triple therapy with 8-week proton pump inhibitor therapy on gastric ulcer healing in infected patients. PATIENTS AND METHODS: We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment. RESULTS: Triple therapy eradicated H. pylori in 51 patients [intention-to-treat, 84%; 95% confidence interval (CI), 75-93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37-62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73-93%, P < 0.001). Healing rates in the triple therapy and proton pump inhibitor-only groups were 89% and 100%, respectively, for ulcers of < 1.0 cm in diameter, 54% and 77% for ulcers of 1.0 to < 1.5 cm in diameter, and 5% and 77% (P < 0.001) for ulcers of > or = 1.5 cm in diameter. CONCLUSIONS: One-week triple therapy healed most ulcers of < 1.0 cm, but not ulcers of > or = 1.5 cm. Short-term therapy is effective for gastric ulcers of < 1.0 cm, but, for larger ulcers, follow-up therapy to suppress acid is needed.     

Will eradication of Helicobacter pylori infection influence the risk of gastric cancer?

Gastric adenocarcinoma is a disease of high mortality and poor prognosis that is second only to lung cancer as a leading cause of cancer-related deaths worldwide. Although gastric cancer has a multifactorial etiology, infection with Helicobacter pylori is highly associated with its development. New information on bacterial and host genetics and results of epidemiologic studies suggest that better identification of individuals at high risk for gastric malignancy may be possible. Studies suggest that cure of H pylori infection may be associated with retardation of glandular atrophy and intestinal metaplasia but not reversal of dysplasia. Theoretically, it is attractive to believe that eradication of H pylori infection might prevent gastric cancer; however, studies supporting this hypothesis are not yet available. Public policy strategies for the identification of patients at risk for H pylori–related gastric malignancy are likely to be complex, but testing and treating for the infection earlier rather than later in life is anticipated to be the more beneficial approach.     

What is the role of serology in assessing Helicobacter pylori eradication?

AIM: To assess the decline in Helicobacter pylori antibodies after eradication of infection. METHODS: The H. pylori status was determined at entry (D0) by culture and histology performed on antral biopsies and after eradication treatment at day 42 (day 42) and after 6 months (M6) by the 13C-urea breath test. The EIA kits used to determine the anti-H. pylori antibody titre were HM-CAP (immunoglobulin-G) and PP-CAP (immunoglobulin-A) kits (Enteric Products, Inc.) and Pyloriset EIA-G (Orion Diagnostica). RESULTS: Ninety-three patients were included. For 82 patients who were successfully treated, no kit was sufficiently accurate at D42 to show eradication. The antibody titre decreased for HM-CAP, PP-CAP and Pyloriset EIA-G by a mean of 35.6%, 41.2% and 64.7% between D0 and M6, respectively. According to the cut-off values defined by the manufacturers, 8.5% (PP-CAP, Pyloriset EIA-G) and 9.7% (HM-CAP) of the patients became H. pylori negative at M6. Using a 25% decrease in antibody titre between D0 and M6 as a threshold for H. pylori eradication, specificity was 100% for HM-CAP, 89.9% for Pyloriset EIA-G and 100% for PP-CAP, whereas the sensitivity was 76.8%, 98.8% and 72%, respectively. CONCLUSION: An antibody titre decrease of 25% at M6 was found to be accurate in confirming H. pylori eradication.     

Would eradication of Helicobacter pylori infection reduce the risk of gastric cancer?

This article reviews the data on the epidemiology of gastric cancer, to determine if treatment of an asymptomatic individual can be justified. It reviews retrospective and prospective case-control studies of gastric cancer in Italy and other countries. Mucosa-associated lymphoid tissue lymphoma is associated with Helicobacter pylori infection. The risk of noncardia gastric cancer is higher (4-fold or greater) in those with H. pylori infection. Although no studies have shown prevention following treatment, eradication of asymptomatic H. pylori infection in an individual in the age group 40 or lower may be expected to reduce the risk of gastric cancer.     

Does seropositivity for Helicobacter pylori antibodies increase outpatient costs for gastric and duodenal ulcer or inflammation?

BACKGROUND: Helicobacter pylori is regarded as an important cause of both peptic ulcer and chronic gastritis. In particular, seropositivity is highest in patients with duodenal ulcer. No studies have determined whether there are differences in the direct medical costs associated with gastric/duodenal ulcer or inflammation, between seropositive and seronegative patients. OBJECTIVE: To examine the relationship between seropositivity for H. pylori and outpatient visits and direct medical costs for gastric/duodenal ulcer or inflammation in Japan from the perspective of the payor and patients. METHODS: Participants were males (n = 653) who worked for an agricultural co-operative in Fukuoka Prefecture, attended an annual health examination (including a written lifestyle and medical survey), belonged to the same health insurance society consistently for 4 years from April 1996 to March 2000, and provided a blood sample. The survey asked about lifestyle, including smoking and drinking, and past medical history. We retrospectively analysed the annual number of outpatient visits per person and outpatient medical cost (Yen, 2000 values) per person for visits relating to gastric or duodenal ulcer or inflammation using International Classification of Diseases (9th edition) -- Clinical Modification codes. We assessed for potential confounding factors using analysis of covariance and the chi-square test. RESULTS: The annual outpatient incidence of disease, the number of visits to physicians, and the medical costs for gastric or duodenal ulcer or inflammation were about 2-fold greater in individuals with antibodies to H. pylori compared with those without antibodies. CONCLUSION: Population-based studies and/or randomised controlled clinical trials that target high-risk groups and account for the unique way in which data are collected in Japan are needed to determine whether medical costs for gastric and duodenal ulcer might be reduced by treating asymptomatic patients who have antibodies to H. pylori.     

Have we found the source of Helicobacter pylori?

Besides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal-oral, oral-oral or gastro-oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.     

Changes in evaluation of the pepsinogen test result following Helicobacter pylori eradication therapy in Japan

Aims The pepsinogen (PG) test result is used in Japan for screening for gastric cancer. In this study, we investigated the changes in evaluation of the PG test result following H. pylori eradication. Methods The subjects were 120 consecutive H. pylori-positive patients with upper gastrointestinal symptoms. Subjects underwent endoscopy prior to, and at 2 months after the eradication therapy, at which time blood was taken for determination of changes in PG levels. Results The overall eradication rate was 79.3 % (per protocol). Following eradication therapy, the evaluation of PG test result converted from positive to negative in 80.4 % (37/46) of cases of successful eradication, and in 0 % (0/6) of cases of eradication failure. Conclusions These results suggest that the evaluation of PG test result should be used after the definitive confirmation of the success or failure of H. pylori eradication therapy. This study was supported by a grant from Tokyo Medical University. Received and accepted 12 July 2006     

Is Helicobacter pylori relevant in the management of reflux disease?

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion. In patients with moderate to severe H. pylori-induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre-existing sub-clinical defective gastro-oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori. There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease. Helicobacter pylori-infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial. Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.     

Is Helicobacter pylori status relevant in the management of GORD?

There is growing interest in the relationship between H. pylori infection and gastro-oesophageal reflux disease (GORD). However, this relationship is complex, as yet not fully elucidated, and probably based on a multiplicity of factors. The prevalence of H. pylori infection in patients with GORD is similar, more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GORD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GORD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GORD. Patients after H. pylori eradication may develop GORD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and pre-existing GORD. H. pylori infected patients treated by various acid-inhibiting therapies such as proton pump inhibitors (PPIs), H2-receptors antagonists (H2-RA) or vagotomy, have an increase of their corpus gastritis severity, both in the activity of inflammation and in the density of organisms. Long-term therapy of GORD in H. pylori infected may lead to rapid progression of atrophic gastritis intestinal metaplasia and dysplasia, and increase the risk of developing gastric cancer. More recently it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GORD. In our opinion the progression of gastritis depends on the threshold of acid output at which H. pylori can 'flourish'. Recently interest is growing on gastric transitional zones and Helicobacter ecology. Any decrease of acid secretion changes the behaviour of H. pylori: the activity of gastritis improves in the antrum, but it deteriorates in the body. During proton pump inhibitor treatment, H. pylori redistribution occurs within the stomach, from an antral to a corpus or fundus prevalent pattern; corpus-fundus gastritis, exacerbated by PPI therapy, may result both in a diminished acid secretion and gastro-oesophageal reflux. The interest in Barrett's oesophagus is growing due to the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's oesophagus patients is not different from that exhibited by controls, roughly one-third of the subjects. Intestinal metaplasia of the gastric cardia seems to be equally frequent in patients with and without GORD. Finally, it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's-associated adenocarcinoma.     

Helicobacter pylori therapy: what is coming?

Despite increasing bacterial resistance to existing drugs, investment in antibacterial discovery and development efforts appears to be flagging. Several factors may play a role in depressing this important area of research, including fragmentation of the antibacterial market, patent expiry and recent confusion within the FDA over how to evaluate new antibacterial candidates. As reflected in patents published in the years 1997 versus 2002, activity in this arena is increasingly focused on novel drug classes and is shifting from large pharmaceutical firms to smaller speciality companies. While this shift favours compounds whose medical need is not matched by a blockbuster market, it may leave the field exposed to overwhelming challenges.     

Metronidazole-based quadruple versus standard triple therapy: which is better as first-line therapy for Helicobacter pylori eradication?

The eradication rate of 7-day standard triple therapy for Helicobacter pylori eradication (a proton pump inhibitor combined with amoxicillin and clarithromycin) has decreased as a consequence of the increase in the resistance rates to clarithromycin. The authors of the article under evaluation conducted a multicenter, randomized, noninferiority, Phase III trial in Europe to compare the efficacy and safety of a 10-day treatment with omeprazole plus a single capsule containing bismuth subcitrate potassium, metronidazole and tetracycline (quadruple therapy) versus a 7-day treatment with omeprazole, amoxicillin and clarithromycin (standard triple therapy) in adults, and demonstrated that the quadruple therapy yielded superior H. pylori eradication rates compared with the standard triple therapy. The results suggest that quadruple therapy merits consideration as first-line eradication therapy for H. pylori in regions with high resistance rates to clarithromycin. However, several issues need to be considered, such as the optimal doses of bismuth and amoxicillin, as well as the treatment duration, before quadruple therapy can be established as the standard first-line therapy for H. pylori eradication.     

Is a one‐week course of triple anti‐Helicobacter pylori therapy sufficient to control active duodenal ulcer?

BACKGROUND: Triple therapy currently forms the cornerstone of the treatment of patients with Helicobacter pylori-positive duodenal ulcer. AIM: To establish whether prolonged antisecretory therapy is necessary in patients with active duodenal ulcer. METHODS: A total of 77 patients with H. pylori-positive duodenal ulcer were included in a prospective, controlled, double-blind study. All patients received a 7-day treatment with omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1000 mg b.d. Patients in the omeprazole group underwent an additional 14-day therapy with omeprazole 20 mg; patients in placebo group received placebo. Endoscopy was performed upon inclusion in the study and after 3 and 8 weeks. RESULTS: Seventy-four patients were eligible for a per protocol analysis after 3 weeks, and 65 after 8 weeks. After 3 weeks, the healing rate was 89% in the omeprazole group and 81% in the placebo group (P=0.51). After 8 weeks, the ulcer healed in 97% of the patients in the total group (95% CI: 92.7-100%). H. pylori was eradicated in 88% of patients in the omeprazole group and in 91% in the placebo group (P=1.0). No statistically significant differences between the groups were found in ulcer-related symptoms or in ulcer healing. CONCLUSION: In patients with H. pylori-positive duodenal ulcer, a 7-day triple therapy alone is sufficient to control the disease.     

Is routine histological evaluation an accurate test for Helicobacter pylori infection?

AIM: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C-urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago-gastro-duodenoscopy. MATERIALS AND METHODS: One-hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C-urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori-positive if two or more tests were positive. RESULTS: Eighty-one patients (70.4%) were found to be H. pylori positive. 13C-urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re-evaluation by an expert pathologist showed a high sensitivity (98. 8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%. CONCLUSION: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre-treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.